Nationwide NIH-Funded Study Probes How Lifelong Environmental Exposures Shape Alzheimer’s Risk

A sweeping national effort to understand how the places people live and work across their entire lives influence their risk of Alzheimer’s disease and related dementias has secured a major second round of federal support. The Neighborhoods Study, led by the University of Wisconsin School of Medicine and Public Health, has been selected for a $30.9 million award from the National Institutes of Health, renewing a collaboration that spans twenty-four Alzheimer’s Disease Research Centers across the United States. Among the key participants is Emory University’s Goizueta Brain Health Institute in Atlanta, which plays an integral role in the study’s design and execution through its Alzheimer’s Disease Research Center.

The study is built around a concept scientists call the social exposome: the cumulative sum of social and environmental factors that a person encounters from birth onward. Rather than focusing on a single risk factor in isolation, the researchers examine how poverty, education, housing, employment, and exposure to toxins accumulate and interact over a lifetime to shape brain health. The central premise is that dementia risk is not determined solely by genes or by individual lifestyle choices, but also by the structural and environmental conditions in which people are embedded for decades before symptoms appear.

What distinguishes The Neighborhoods Study from other large dementia research programs is its scale and its unusual reach into biology. It is the largest study in the world to connect the social exposome with actual brain tissues and their disease biomarkers. This means the project does not stop at survey data or neighborhood statistics; it links lifelong exposure histories to measurable changes in the brain, including the molecular hallmarks of Alzheimer’s disease and related dementias that can be detected in tissue. By bridging the social sciences and neuropathology, the collaboration aims to uncover the precise mechanisms by which adverse environments translate into neurodegeneration.

With the renewed funding, the investigators will expand their focus to several specific exposure domains. The next phase of research will assess lead-contaminated infrastructure exposure, job-related toxin exposures that people accumulate throughout their working lives, and the presence of heavy metals in brain tissue. These lines of inquiry are designed to clarify what makes certain populations especially vulnerable to Alzheimer’s disease and related dementias, and to determine whether toxic exposures that vary by occupation, housing quality, and geography leave detectable signatures in the brain that correlate with disease outcomes.

Allan Levey, MD, PhD, director of the Emory Goizueta Alzheimer’s Disease Research Center and executive director of the Emory Goizueta Brain Health Institute, emphasized the preventive promise of the work. By examining how social and environmental factors accumulate across the lifespan and influence brain health, he said, researchers have an important opportunity to identify ways to reduce risk and to develop more effective and equitable approaches to prevention. He described the study as the kind of collaborative, interdisciplinary research that is essential to understanding and ultimately preventing Alzheimer’s disease and related dementias, and noted that Emory is proud to contribute to the national effort through its Alzheimer’s Disease Research Center.

Felicia Goldstein, PhD, professor of neurology at Emory University, co-lead of the Clinical Core of the Emory Alzheimer’s Disease Research Center, and Emory site principal investigator for The Neighborhoods Study, highlighted the scientific value of connecting lived experience to brain biology. She said the research offers an important opportunity to understand how the environments in which people live and work over the course of their lives can influence brain health and dementia risk. By linking these lifelong exposures with brain changes and disease biomarkers, she explained, the team can move closer to identifying the populations at greatest risk and developing more precise strategies for prevention and risk reduction.

The renewed award builds on substantial achievements from the study’s first phase, which was initiated in 2021. That phase supported the continued development of the Area Deprivation Index, a tool created at the University of Wisconsin’s Center for Health Disparities Research that ranks neighborhoods by socioeconomic disadvantage. The ADI has since been used to develop thousands of health interventions and policies aimed at achieving better health outcomes for people living in rural and urban neighborhoods with the greatest need, making it one of the most widely applied measures of neighborhood disadvantage in American health research.

The first phase of The Neighborhoods Study also produced important scientific findings in its own right. The researchers demonstrated an association between neighborhood disadvantage, as measured by the Area Deprivation Index, and increased odds of neurodegeneration, Alzheimer’s disease biomarkers, and post-mortem neuropathology of the disease. They further linked residency in high-ADI neighborhoods across a person’s lifetime with increased risk of neurodegeneration and brain disease. Together, these results suggest that the cumulative burden of living in disadvantaged environments is written into the brain itself, visible both in biomarkers during life and in pathological changes after death.

Looking ahead, the study is expected to facilitate prevention measures for Alzheimer’s disease and related dementias that are precisely tailored to the populations at highest risk based on their specific exposure profiles. Rather than offering generic advice, such tailored interventions could target the particular environmental hazards and social conditions that drive risk in a given community, whether those involve lead-contaminated water systems, occupational toxin exposure, or concentrated neighborhood poverty. The work focuses on risk mitigation and the development of new interventions, advancing knowledge of the relationship between the exposome and dementia in order to improve health for all.

The significance of the effort extends beyond any single institution. Alzheimer’s disease and related dementias represent one of the largest and fastest-growing public health challenges of an aging global population, and decades of research have shown that no single cause explains the majority of cases. By coordinating twenty-four research centers under a common framework and tying social data to brain tissue analysis, The Neighborhoods Study offers a model for how large-scale, interdisciplinary science can address complex diseases whose roots lie partly in the social and physical world. For the Emory Goizueta Brain Health Institute, which is dedicated to advancing innovation in brain health prediction, prevention, and treatment, participation in the study reflects its broader mission to uncover the mechanisms of brain disease and to develop therapeutic strategies and biomarkers that can change the trajectory of dementia for the communities most affected.

Subject of Research: The relationship between lifelong social and environmental exposures and Alzheimer's disease risk

Article Title: Emory Goizueta Brain Health Institute part of nationwide NIH study on links between environmental factors and Alzheimer's disease

Article References: Emory Goizueta Brain Health Institute part of nationwide NIH study on links between environmental factors and Alzheimer's disease. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Alzheimer's disease, social exposome, NIH funding, neighborhood disadvantage, Area Deprivation Index, dementia prevention, brain biomarkers, heavy metals, lead exposure, Emory University, neurodegeneration, public health